Check thisWays to make acoustic cavitation predictable, and thus practical as a mechanism for noninvasive surgery, will be explored in this research. Novel ways to accurately place therapy beams and verifying that surgical lesions have been formed will also be explored. With the use of large aperture phased array systems, and aberration correction techniques, it is possible to form high quality ultrasound beams around and through obstructions like ribs, or the skull, with the attractive possibility of noninvasive brain surgery or cardiac ablation for treatment of life threatening arrhythmias. With the loss of energy in propagating around and through such obstructions, thermal ablation, without heating the complex intervening tissue, is a difficult proposition. However, cavitation, particularly from arrays operating at lower ultrasound frequencies, becomes an exciting tissue ablation mechanism for further study. Of particular interest is the potential use of stabilized microbubbles, often used as ultrasound imaging contrast agents, to act as cavitation nuclei lowering cavitation thresholds and making spatial localization predictable. Cavitation has been intentionally avoided in the past because reproducible localization of ablation zones (or surgical lesions) has been difficult mostly due to large unpredictable spatial variations in cavitation thresholds in living tissues. Preliminary experiments with phased array systems suggest that surgical lesion size and shape become more predictable with prior administration of contrast agents. The applicants proposed to systematically explore the role of contrast agents on cavitation thresholds, surgical lesion size and histology, predictability of shape and spatial localization of necrotic zones, and role of contrast agent concentration. Such systems will allow highly predictable beams to be formed non-invasively, for example, around the ribs onto a moving target, e.g. the heart. Contrast agents will also be explored as means for targeting therapy beams and as a way to verify that surgical lesions have been formed in the desired treatment volume. This application is based on their experimental observation that microbubbles can be "collapsed" by low intensity ultrasound causing "darker" areas in the image, thus allowing sub-lesion forming intensities to be used for beam localization prior to application of surgical intensities. Since cavitationally induced lesions will likely destroy the local vasculature, a surgically necrosed volume will not re-perfuse with contrast agent indicating lesion extent. The applicants will explore use of contrast agents as means to guide, enhance, and verify surgical lesion formation with high intensity ultrasound.